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The primary characteristics of a clinical assay are its accuracy and speed. For alkaline phosphatase (ALP) monitoring in medical treatment, a rapid, reliable surface-enhanced Raman scattering (SERS) detection technique was designed based on the controlled "hot spot" effect caused by the mediation of silver ions (Ag + ). Consisting of functionalized Au nanoparticles (NPs), Ag + , and the enzyme substrate 2-phospho-L-ascorbic acid triso-dium salt (AAP), the fabricated detection technique can achieve a reliable clinical assay for ALP detection in human serum within several minutes. Herein, due to the coordination interaction of Ag + and the cyano group (-CN), Ag + can coordinate with p -mercaptobenzonitrile (MBN) modified on the surface of Au NPs, leading to the connection of adjacent Au NPs in a controllable manner to form a chain structure, in which the SERS signal of MBN at 2228 cm -1 in the Raman silent region would be highly amplified. Under the enzymatic biocatalysis of ALP, AAP was converted into ascorbic acid (AA). AA triggered the reduction of Ag + into Ag 0 , resulting in a decrease in the concentration of Ag + . Meanwhile, the decrease in the SERS intensity of MBN was well-controlled and was recognized with the increased amounts of ALP. Based on this, the SERS detection technique for ALP was established. The limit of detection (LOD) for the detection of ALP was as low as 1.23 pg mL -1 (0.005 U L -1 ). Because of all these characteristics and its ultrahigh stability, this SERS detection technique is an important point-of-care candidate for the reliable, efficacious, and highly sensitive detection of ALP.

Background: Sickle cell disease (SCD) is a genetic blood disorder characterized by a painful vaso-occlusive crisis due to the sickling of red blood cells in capillaries. Complications often lead to liver and renal dysfunctions, contributing to morbidity and mortality, particularly for children under 5. This systematic review and meta-analysis aimed to evaluate the liver and renal functions of people with SCD (HbSS) compared to those without it (HbAA) in Africa., Methods: The protocol was registered with PROSPERO (CRD42022346771). We searched PubMed, Embase, Web of Science, and Google Scholar using the keywords "liver function", "renal function", "sickle cell disease", and "Africa" on 6th May 2023 for peer-reviewed articles with abstracts in English. We included case-control studies comparing SCD (HbSS) with controls without hemoglobinopathies (HbAA). We used the random-effect model to calculate the pooled average values for the blood tests of people with SCD in RStudio version 4.2.2., Results: Overall, 17 articles were analyzed from five African countries involving 1312 people with SCD and 1558 controls. The pooled mean difference of liver enzymes aspartate transaminase (AST) was 8.62 (95% CI - 2.99-20.23, I 2  = 97.0%, p < 0.01), alanine transaminase (ALT) 7.82 (95% CI - 0.16-15.80, I 2  = 99%, p < 0.01) and alkaline phosphatase (ALP) - 2.54 (95% CI - 64.72 - 59.64, I 2  = 99%, p < 0.01) compared to controls. The pooled mean difference for the renal biochemical profiles creatinine - 3.15 (95% CI - 15.02; 8.72, I 2 =99%, p < 0.01) with a funnel plot asymmetry of t = 1.09, df = 9, p = 0.3048 and sample estimates bias of 6.0409. The pooled mean difference for serum urea was - 0.57 (95% CI - 3.49; 2.36, I 2  = 99%, p < 0.01), and the estimated glomerular filtration (eGFR) rate was 19.79 (95% CI 10.89-28.68 mL/min/1.73 m 2 , I 2  = 87%, p < 0.01) compared to controls., Conclusion: People with SCD have slightly elevated liver enzymes and estimated glomerular filtration rates compared to controls in Africa. With all the heterogeneity (I 2 ) > 50%, there was substantial variation in the reported articles' results., Systematic Review Registration: PROSPERO CRD42022346771., (© 2024. The Author(s).)

A metal-organic-framework (MOF) fluorescent sensor is reported based on NH 2 -MIL-101(Fe) propelled pesticide and alkaline phosphatase (ALP) catalytic reaction. Different from previous reports, a cascade reaction system combined with MOF structural changes to generate fluorescence was employed. The rationale is that ALP can hydrolyze L-ascorbic acid 2-phosphate (AAP) into L-ascorbic acid (AA), which can reduce Fe 3+ to decompose structurally NH 2 -MIL-101(Fe), resulting in 2-aminoterephthalic acid (NH 2 -BDC) with intense fluorescence. The  fluorescence can be decreased to different degrees due to inhibition of organophosphate pesticides (OPPs) on the activity of ALP. By taking chlorpyrifos (CPY) as the model compound of an OPP pesticide and adding ALP and CPY into the NH 2 -MIL-101(Fe) framework, the resulting cascade reaction fluorescence sensors exhibit a good sensitivity for CPY and ALP sensing. The working ranges are  0.02-2 μg/L and 0.2-20 mU/mL with detection limits (LOD) of 5.31 ng/L and 0.05 mU/mL, respectively. The proposed sensor has been actually applied to satisfactory detection of CPY and ALP in food and serum samples. This fluorescence-based assay may extend the application of MOF-based biosensors., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Background/objectives: Antrodia camphorata , also known as "Niuchangchih" in Taiwan, is a unique medicinal mushroom native to Taiwan. It is used in traditional medicine to treat various health conditions. In this study, we investigated the efficacy of A. camphorata mycelia on alcohol-induced liver damage, both in vitro and in vivo, in a Good Laboratory Practice (GLP) facility., Methods: The experimental groups consisted of a normal control group (G1), a negative control group (G2), an A. camphorata mycelium powder 50 mg/kg/day administration group (G3), a 100 mg/kg/day administration group (G4), a 200 mg/kg/day administration group (G5), and a positive control silymarin 200 mg/kg/day administration group (G6), with 10 Sprague Dawley rats assigned to each treatment group., Results: We found that treatment with A. camphorata mycelium powder significantly reduced alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, cholesterol, adiponectin, triglyceride, and malondialdehyde concentrations. Histopathological analysis also revealed that the inflammation score significantly decreased in the A. camphorata -treated groups., Conclusion: Based on these results, we conclude that repeated oral administration of A. camphorata mycelium powder is effective in improving alcoholic liver disease.

Data on cholestasis and biliary injury in patients with COVID-19 are scarce. The primary aim of this study was to evaluate the prevalence of cholestasis and factors associated with its development and outcome in critically ill patients with COVID-19 associated acute respiratory distress syndrome (ARDS). In this retrospective exploratory study, COVID-19 patients with ARDS admitted to an intensive care unit (ICU) at the Medical University of Vienna were evaluated for the development of cholestasis defined as an alkaline phosphatase level of 1.67x upper limit of normal for at least three consecutive days. Simple and multiple logistic regression analysis was used to evaluate parameters associated with development of cholestasis and survival. Of 225 included patients 119 (53%) developed cholestasis during ICU stay. Patients with cholestasis had higher peak levels of alkaline phosphatase, gamma-glutamyl transferase, bilirubin and inflammation parameters. Factors independently associated with cholestasis were extracorporeal membrane oxygenation support, ketamine use, high levels of inflammation parameters and disease severity. Presence of cholestasis and peak ALP levels were independently associated with worse ICU and 6-month survival. Development of cholestasis is a common complication in critically ill COVID-19 patients and represents a negative prognostic marker for survival. It is associated with disease severity and specific treatment modalities of intensive care., (© 2024. The Author(s).)

Objective: To evaluate the workplace health-related environment of workers in various job categories at a cement factory., Methods: The cross-sectional study was conducted at the Kufa Cement Factory, Najaf, Iraq, from November 12, 2021, to January 12, 2022 and comprised adult male non-smoking factory workers in group A, and healthy, unexposed non-smokers in control group B. Subjects in group A were subdivided into factory, kiln and packing workers. All the participants were subjected to blood tests for liver and kidney functions. Data was analysed using SPSS 27., Results: Of the 90 subjects, 45(50%) were each of the 2 groups. The mean age of group A workers was 46.581±1.559 years and they had a mean duration of exposure 15.953±0.873 years. There were 15(33.3%) factory workers and as many kiln and packing workers. Group A subjects worked for at least 7-8 hours per day. The subjects in control group B had a mean age of 45.01±8.17 years and were matched for gender. There was significant elevation in total leukocyte count, alkaline phosphatase, aspartate aminotransferase and alanine aminotransferase in group A compared to group B (p<0.05). Neutrophils were significantly high in factory workers than controls and packing workers (p<0.05), while total bilirubin level was significantly high in factory and kiln workers than controls (p<0.05). There was no significant difference in the mean serum creatinine level between the groups (p>0.05)., Conclusions: Workplace exposure to cement particulate in a factory environment was found to have a harmful impact on health.

Objective: To assess the hepatoprotective effect of curcumin and/or vitamin C in methotrexate-induced hepatotoxicity., Methods: The experimental study was conducted at the Department of Pharmacology, College of Medicine, and the Iraqi Centre for Cancer and Medical Genetic Research, Mustansiriya University, Baghdad, Iraq, from Nov 12, 2020, to June 1, 2021, and comprised Swiss albino female mice aged 3-4 months and weighing 30-40g each. The mice were divided into 5 groups and treated for 10 days. Group 1 received distilled water, group 2 received single-dose methotrexate on the 10th day of the trial, group 3 was treated with curcumin plus methotrexate, group 4 was treated with vitamin C plus methotrexate, and group 5 was treated with curcumin and vitamin C plus methotrexate. Parameters measured were serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and lactate dehydrogenase, as well as hepatic tissue malondialdehyde, superoxide dismutase and glutathione. Data was analysed using SPSS 16., Results: There were 35 mice; 7(20%) in each of the 5 groups. Hepatoprotection produced by curcumin as reflected by a decrease in lactate dehydrogenase and malondialdehyde levels was significant (p<0.05). Vitamin C also produced a significant hepatoprotection, demonstrated by a decrease in alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase and malondialdehyde levels. The combination of curcumin and vitamin C reflected an additive effect demonstrated by a significant decrease in malondialdehyde (p<0.05)., Conclusions: Curcumin and/or vitamin C provided hepatoprotection against methotrexate-induced hepatotoxicity through modulation of oxidative stress biomarkers.

In this work, a novel and sensitive fluorescence sensing system for alkaline phosphatase (ALP) was constructed using a bifunctional copper metal-organic framework (Cu@MOF) nanozyme, which had excellent oxidase-mimetic activity and fluorescence properties. Owing to the presence of 2-amino-1,4-benzenedicarboxylic acid (1,4-BDC-NH 2 ) ligand, Cu@MOF displays excellent fluorescence performance at 444 nm. Additionally, Cu 2+ endows the oxidase-like activity of Cu@MOF, which could trigger p-phenylenediamine (PPD) to be oxidized to a brown product (PPDox) and quench the photoluminescence of Cu@MOF through the inner filtration effect (IFE). As the preferential affinity of ATP for Cu 2+ , the catalytic activity of Cu@MOF was significantly reduced once ATP was added, thus PPD could not be oxidized and fluorescence was recovered. In the presence of ALP, ATP was hydrolyzed to adenosine and Pi, which allowed Cu@MOF to regain its catalytic activity and continued to catalyze the generation of PPDox. The fluorescence of Cu@MOF was therefore weakened once again. The ALP activity was directly proportional to the degree of decrease in fluorescence intensity. Thus, this novel fluorescence sensing strategy had a linear range of 0.5-60 U/L and the limit of detection was 0.14 U/L. The established sensing method could also be used to for ALP inhibitors screening, and achieved satisfactory results in determining the level of ALP activity in human serum., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Primary biliary cholangitis is a chronic and progressive autoimmune liver disease, whose prognosis can be improved by normalizing alkaline phosphatase and bilirubin. While ursodeoxycholic acid (UDCA) is first line standard of care, approximately 40 % of patients exhibit incomplete response. We aimed to identify prognostic markers for deep response to UDCA therapy at presentation., Patient and Methods: Data from the Brazilian Cholestasis Study Group cohort were analyzed retrospectively. Patients were assessed for deep response, defined as normal alkaline phosphatase and bilirubin, after 1 year of UDCA treatment. Additionally, the performance of the UDCA response score in predicting deep response was evaluated., Results: A total of 297 patients were analyzed, with 57.2 % achieving an adequate response according to the Toronto criteria, while 22.9 % reached deep response. Cirrhosis (OR 0.460; 95 % CI 0.225-0.942; p = 0.034) and elevated baseline alkaline phosphatase levels (OR 0.629; 95 % CI 0.513-0.770; p < 0.001) were associated with reduced odds of deep response. The UDCA response score exhibited moderate discrimination power (AUROC = 0.769) but lacked calibration., Conclusions: Baseline ALP and liver fibrosis emerge as the most important prognostic factors to predict normalization of alkaline phosphatase and bilirubin after UDCA. The UDCA response score was inadequate for predicting deep response in the Brazilian PBC population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

This study introduces an innovative approach for the real-time and efficient detection of alkaline phosphatase (ALP) activity, using a calcein fluorescence probe and leveraging the static quenching properties of calcein fluorescence by Ce 3+ metal ions. In this method, calcein serves as the signal element, with its fluorescence effectively preserved through energy transfer or charge transfer when coordinated with Ce 3+ . Conversely, ALP catalyzes the phosphopeptide substrate to generate a substantial amount of Pi, preventing calcein fluorescence quenching due to the higher affinity between Pi and Ce 3+ compared with that between calcein and Ce 3+ . The fluorescence intensity ratio (F-F 0 /F 0 ) exhibited excellent linearity, facilitating sensitive ALP detection. The proposed ALP detection method covers a range from 0 to 1.4 mU/mL (R 2  = 0.9942), with the limit of detection at 0.069 mU/mL (S/N = 3). Additionally, this method was successfully applied for detecting ALP in serum samples and studying its inhibitors. This research introduces a novel clinical diagnosis approach for ALP sensing while broadening the potential applications of calcein., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Background & Aims: Recurrent primary biliary cholangitis (rPBC) develops in approximately 30% of patients and negatively impacts graft and overall patient survival after liver transplantation (LT). There is a lack of data regarding the response rate to ursodeoxycholic acid (UDCA) in rPBC. We evaluated a large, international, multi-center cohort to assess the performance of PBC scores in predicting the risk of graft and overall survival after LT in patients with rPBC., Methods: A total of 332 patients with rPBC after LT were evaluated from 28 centers across Europe, North and South America. The median age at the time of rPBC was 58.0 years [IQR 53.2-62.6], and 298 patients (90%) were female. The biochemical response was measured with serum levels of alkaline phosphatase (ALP) and bilirubin, and Paris-2, GLOBE and UK-PBC scores at 1 year after UDCA initiation., Results: During a median follow-up of 8.7 years [IQR 4.3-12.9] after rPBC diagnosis, 52 patients (16%) had graft loss and 103 (31%) died. After 1 year of UDCA initiation the histological stage at rPBC (hazard ratio [HR] 3.97, 95% CI 1.36-11.55, p = 0.01), use of prednisone (HR 3.18, 95% CI 1.04-9.73, p = 0.04), ALP xULN (HR 1.59, 95% CI 1.26-2.01, p <0.001), Paris-2 criteria (HR 4.14, 95% CI 1.57-10.92, p = 0.004), GLOBE score (HR 2.82, 95% CI 1.71-4.66, p <0.001), and the UK-PBC score (HR 1.06, 95% CI 1.03-1.09, p <0.001) were associated with graft survival in the multivariate analysis. Similar results were observed for overall survival., Conclusion: Patients with rPBC and disease activity, as indicated by standard PBC risk scores, have impaired outcomes, supporting efforts to treat recurrent disease in similar ways to pre-transplant PBC., Impact and Implications: One in three people who undergo liver transplantation for primary biliary cholangitis develop recurrent disease in their new liver. Patients with recurrent primary biliary cholangitis and incomplete response to ursodeoxycholic acid, according to conventional prognostic scores, have worse clinical outcomes, with higher risk of graft loss and mortality in similar ways to the disease before liver transplantation. Our results supportsupport efforts to treat recurrent disease in similar ways to pre-transplant primary biliary cholangitis., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study investigated the impact of wheat processing methods (wheat flour vs wheat pellets) on the growth performance, serum biochemical parameters, and rumen microbiome composition in sheep. Results indicated that feeding of wheat flour resulted in significantly higher terminal weight and average daily gain (P < 0.05) and lower cholesterol and ALP04 levels (P < 0.05) in sheep compared to those fed wheat pellets. Analysis of 16s rDNA high-throughput sequencing data revealed significantly higher microbial richness (Chao1 index) in the rumen of sheep fed wheat flour (P < 0.05), even though the phylum-level composition dominated by Firmicutes, Bacteroidetes, and Proteobacteria was similar in both groups of sheep. Notably, sheep fed wheat flour were found to have a significantly higher relative abundance of Bacteroidetes (P < 0.05). At the genus level, Succinivibrionaceae&#95;UCG-001 and Prevotella&#95;1 were significantly more abundant in the rumen of sheep fed wheat flour (P < 0.05). Correlation analysis identified that both terminal weight and average daily gain were positively correlated with ruminal abundance of Bacteroidetes and Prevotella&#95;1, while ALP04 was negatively correlated with the abundance of these taxa. Functional prediction using PICRUSt2 indicated enrichment of pathways related to the ABC-type glycerol-3-phosphate transport system, and periplasmic components in both wheat flour and pellet fed sheep. Overall, these findings suggest that dietary wheat flour modulates rumen microbiota composition, and improves growth performance in sheep., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Hypophosphatasia (HPP) is a rare, inherited metabolic disease caused by deficient activity of tissue-nonspecific alkaline phosphatase (TNSALP). Efzimfotase alfa (ALXN1850) is a second-generation TNSALP enzyme replacement therapy in development for HPP. This first-in-human open-label, dose-escalating phase 1 trial evaluated efzimfotase alfa safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity. Fifteen adults (5/cohort) with HPP received efzimfotase alfa in doses of 15 mg (cohort 1), 45 mg (cohort 2), or 90 mg (cohort 3) as one intravenous (i.v.) dose followed by 3 weekly subcutaneous (s.c.) doses. The primary objective was to assess safety and tolerability. Secondary objectives included pharmacokinetics, pharmacodynamics of ALP substrates known to be biomarkers of disease (inorganic pyrophosphate [PPi] and pyridoxal 5'-phosphate [PLP]) and immunogenicity. Treatment-emergent adverse events (TEAEs) occurred in 12 (80%) participants. Eight (53%) participants had injection site reactions (ISRs), observed after 10 of 41 (24%) s.c. injections. Most ISR TEAEs were mild and resolved within 1-2 d. Peak and total exposures of efzimfotase alfa increased in a greater-than-dose proportional manner over the range of 15-90 mg after i.v. and s.c. dosing. The arithmetic mean elimination half-life was approximately 6 d; absolute bioavailability was 28.6%-36.8% over the s.c. dose range of 15-90 mg. Dose-dependent reductions in plasma concentrations of PPi and PLP relative to baseline reached nadir in the first week after i.v. dosing and were sustained for 3-4 wk after the last s.c. dose. Four (27%) participants tested positive for antidrug antibodies (ADAs), 3 of whom were ADA positive before the first dose of efzimfotase alfa. ADAs had no apparent effect on efzimfotase alfa pharmacokinetics/pharmacodynamics. No participants had neutralizing antibodies. Efzimfotase alfa demonstrated acceptable safety, tolerability, and pharmacokinetic profiles and was associated with sustained reductions in biomarkers of disease in adults with HPP, supporting further evaluation in adult and pediatric patients. Registration: ClinicalTrials.gov NCT04980248 (https://clinicaltrials.gov/study/NCT04980248)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the American Society for Bone and Mineral Research.)

Portal vein tumor thrombosis (PVTT) is one of the common complications of HCC and represents a sign of poor prognosis. PVTT signifies advanced liver cancer, deteriorating liver function, and heightened susceptibility to intrahepatic dissemination, systemic metastasis, and complications related to portal hypertension. It is important to seek novel strategies for PVTT arising from HCC. Portal vein tumor thrombus (PVTT) in hepatocellular carcinoma (HCC) represents a worse liver function, less treatment tolerance, and poor prognosis. This study aimed to investigate the diagnostic value of the combination of the DeRitis ratio (AST/ALT) and alkaline phosphatase (ALP) index (briefly named DALP) in predicting the occurrence risk of PVTT in patients with HCC. We performed a retrospective study enrolling consecutive patients with HCC from January 2017 to December 2020 in Hebei Medical University Third Hospital. ROC analysis was performed to estimate the predictive effectiveness and optimal cut-off value of DALP for PVTT occurrence in patients with HCC. Kaplan-Meier analysis revealed the survival probabilities in each subgroup according to the risk classification of DALP value. Univariate and multivariate Logistics regression analyses were applied to determine the independent risk for poor prognosis. ROC analysis revealed that the optimal cut-off value for DALP was 1.045, with an area under the curve (AUC) of 0.793 (95% CI 0.697-0.888). Based on the DALP classification (three scores: 0-2) with distinguishable prognoses, patients in the score 0 group had the best prognosis with a 1-year overall survival (OS) of 100%, whereas score 2 patients had the worst prognosis with 1-year OS of 72.4%. Similarly, there was a statistically different recurrence-free survival among the three groups. Besides, this risk classification was also associated with PVTT progression in HCC patients (odds ratio [OR] 5.822, P < 0.0001). Pathologically, patients in the score 2 group had more advanced tumors considering PVTT, extrahepatic metastasis, and ascites than those in score 0, 1 groups. Moreover, patients with a score of 2 had more severe hepatic inflammation than other groups. Combination of DeRitis ratio and ALP index presented a better predictive value for PVTT occurrence in patients with HCC, contributing to the tertiary prevention., (© 2024. The Author(s).)

Transient hyperphosphatasemia (TH) is a benign condition observed among healthy infants and children < 5 years old. It is characterized by an elevation in serum alkaline phosphatase (ALP) in the absence of other signs of organ disease. Prognosis is excellent, and ALP levels stabalize within 4 months. The aim of this case report is to promote broader awareness of TH so further unnecessary workup is avoided. The patient was a 12-month-old girl who presented with pale stools, a single episode of bloody stool, and elevation (incidentally found) in her ALP of 2379 IU/L. A small anal fissure was present, and the remainder of her physical examination was typical. The differential diagnosis included biliary atresia, liver disease, bone disease, and TH. Further testing was typical and included complete blood count (CBC, consisting of hemoglobin, hematocrit, white blood cell count, and platelet count), comprehensive metabolic panel (CMP, consisting of glucose, creatinine, BUN, electrolytes, and liver function markers), calcium, phosphate, parathyroid hormone, gamma-glutamyl transferase, and 25-hydroxy vitamin D. Liver ultrasound was also typical without evidence of biliary atresia. The diagnosis of TH was made. The patient was monitored clinically. Repeat blood work was completed 2 months later, with ALP levels returning to the typical range. Overall, TH is a benign self-limiting condition that can be managed by observation and serial measurement of ALP without further unnecessary investigations., Competing Interests: Conflicts of Interest None declared

Background: Acute liver failure (ALF) following cardiac arrest (CA) poses a significant healthcare challenge, characterized by high morbidity and mortality rates. This study aims to assess the correlation between serum alkaline phosphatase (ALP) levels and poor outcomes in patients with ALF following CA., Methods: A retrospective analysis was conducted utilizing data from the Dryad digital repository. The primary outcomes examined were intensive care unit (ICU) mortality, hospital mortality, and unfavorable neurological outcome. Multivariable logistic regression analysis was employed to assess the relationship between serum ALP levels and clinical prognosis. The predictive value was evaluated using receiver operator characteristic (ROC) curve analysis. Two prediction models were developed, and model comparison was performed using the likelihood ratio test (LRT) and the Akaike Information Criterion (AIC)., Results: A total of 194 patients were included in the analysis (72.2% male). Multivariate logistic regression analysis revealed that a one-standard deviation increase of ln-transformed ALP were independently associated with poorer prognosis: ICU mortality (odds ratios (OR) = 2.49, 95% confidence interval (CI) 1.31-4.74, P = 0.005), hospital mortality (OR = 2.21, 95% CI 1.18-4.16, P = 0.014), and unfavorable neurological outcome (OR = 2.40, 95% CI 1.25-4.60, P = 0.009). The area under the ROC curve for clinical prognosis was 0.644, 0.642, and 0.639, respectively. Additionally, LRT analyses indicated that the ALP-combined model exhibited better predictive efficacy than the model without ALP., Conclusions: Elevated serum ALP levels upon admission were significantly associated with poorer prognosis of ALF following CA, suggesting its potential as a valuable marker for predicting prognosis in this patient population., (© 2024. The Author(s).)

In this work, an optimal air supply mode was selected to create a model of cerebral arterial air embolism (CAAE) on conscious male Sprague-Dawley rats (n=49). The efficacy of the selected model (administration of 100 μl/kg of air at a rate of 10 μl/min with an infusion pump) was determined by changes in serum biochemical parameters (cholesterol, alkaline phosphatase, inorganic phosphates, AST, and triglycerides), impaired motor functions in the Rotarod test, and visual assessment of the ischemic foci (staining of frontal sections with 1% triphenyltetrazolium chloride solution) at different terms after AAE. The model of AAE created by us confirmed impairment of coordination and motor function in conscious animals and reproduced the lethal consequences of this condition. The obtained results can serve as the basis for drug testing and the development of new approaches to the treatment of ischemic stroke., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

The purpose of this study was to observe the changes in bone-specific alkaline phosphatase (B-ALP) and tartrate-resistant acid phosphatase-5b (TRAP-5b) in a patient diagnosed with short root anomaly (SRA). The detailed clinical data and history of related clinical symptoms of the SRA patient were retrieved. Oral examination showed that the shape and color of the tooth crown were normal. Tooth 11 and 12 were missing, and the mobility degree of other teeth was II-III. Panoramic radiograph examination showed that the root length only reached the neck of the tooth. Laboratory results showed that blood spectrum, chromosome and trace elements were normal. Endocrinological evaluation indicated that hormone levels were within normal limits; however, both B-ALP and TRAP-5b were higher than the normal range. The present case shows that SRA may be related to an imbalance in osteoblast/osteoclast metabolism, which provides a new direction for the etiological research of this disease., Competing Interests: The authors declare no conflict of interest., (©2024 The Author(s). Published by MRE Press.)

Purpose: This aim of this study was to assess the possible association between diurnal oscillations and biochemical markers associated with calcium homeostasis. This included the markers parathyroid hormone (PTH), total calcium, total alkaline phosphatase, phosphate, and 25-hydroxyvitamin D (25-OH-D). By examining the influence of circadian rhythms on these parameters, the study aimed to deepen the understanding of calcium metabolism dynamics and its clinical implications., Patients and Methods: Blood samples from 24 Caucasian male volunteers aged 20 to 40 (mean age 26) with normal pulse, blood pressure, and BMI were analyzed for biochemical markers related to calcium homeostasis. Data was obtained from the Bispebjerg study of diurnal variations. Blood samples were collected every three hours over a 24-hour period. Patients were fasting from 22:00 to 09:00. The participants spent 24 h in the hospital ward, receiving regular meals and engaging in low-intensity activities. They experienced 15 h of daylight and 9 h of complete darkness during sleep. Diurnal oscillations were analyzed using cosinor analysis with statistical significance set at p  < 0.05., Results: Total calcium, phosphate, and PTH exhibited significant diurnal variations. Total calcium and PTH were inversely synchronized while PTH and phosphate oscillated in synchronization. The three parameters showed relatively large amplitude/reference range ratios from 25.4% to 41.5%., Conclusion: This study found notable fluctuations in total calcium, phosphate, and PTH levels over a 24-hour cycle, while 25-OH-D and total alkaline phosphatase remained consistent. It highlights the importance of considering sampling times for total calcium, PTH, and phosphate in clinical settings.

Introduction: To investigate the clinical value of serum albumin to alkaline phosphatase ratio (AAPR) in predicting the risk of osteoporotic vertebral refractures group (OVRFs) after percutaneous vertebral augmentation (PVA) in postmenopausal women., Materials and Methods: This is a retrospective case-control study including a series of postmenopausal women patients with osteoporotic vertebral fracture (OVF) and underwent PVA. Patients were divided into OVRFs and non-OVRFs. COX model was used to evaluate the correlation between preoperative AAPR and OVRFs after PVA. The receiver operating characteristic (ROC) curve and Kaplan-Meier method were used to analyze the predictive value of AAPR for the incidence of OVRFs., Results: A total of 305 patients were included in the final study, and the incidence of postoperative OVRFs was 28.9%. Multivariate COX analysis showed that advanced age (HRs = 1.062, p = 0.002), low BMI (HRs = 0.923, p = 0.036), low AAPR (HRs = 0.019, p = 0.001), previous fall history (HRs = 3.503, p = 0.001), denosumab treatment (HRs = 0.409, p = 0.007), low L3 BMD (HRs = 0.977, p = 0.001) and low L3 paravertebral muscle density (PMD)value (HRs = 0.929, p = 0.001)) were closely related to the incidence of OVRFs. The area under the curve (AUC) of AAPR for predicting OVRFs was 0.740 (p < 0.001), and the optimal diagnostic cut-off value was 0.49. Kaplan-Meier curve analysis showed that low AAPR group (< 0.49) was significantly associated with lower OVRFs-free survival (p = 0.001; log-rank test)., Conclusion: AAPR is an independent risk factor for OVRFs after PVA in postmenopausal women, and it can be used as an effective index to predict OVRFs., (© 2024. The Japanese Society Bone and Mineral Research.)

Purpose: The primary goal was to estimate reference values of parathyroid hormone (PTH) in very low birth weight infants without severe neonatal morbidity. A secondary objective was to assess the relationship between PTH serum levels and selected laboratory markers of bone metabolism., Methods: Ninety two infants with birth weight less than 1500 g met the inclusion criteria of the study. Serum levels of PTH, 25-hydroxyvitamin-D [25(OH)D], C3-epi-25(OH)D, total calcium, phosphorus, and alkaline phosphatase, and urinary levels of calcium, phosphorus, and creatinine were examined on day 14 and subsequently every 2 weeks until discharge., Results: Of the total 167 serum samples examined for PTH levels in infants without 25(OH)D deficiency the estimated range was 0.9-11.9 pmol/l (8.5-112.3 pg/mL). During the first month, no statistically significant correlation was observed between PTH level and that of 25(OH)D, C3-epimers of 25(OH)D, S-Ca, S-P, or ALP, nor with urinary excretion of calcium and phosphorus. From the second month of life, there was a moderately significant correlation between PTH and 25(OH)D (Rho = -0.40, P =< .001), between PTH and calcium/creatinine ratio (Rho = -0.56, P = < .001), and between PTH and phosphorus/creatinine ratio (Rho = 0.51, P = < .001)., Conclusions: The physiological range for PTH levels for preterm neonates without 25(OH)D deficiency was estimated as 0.9-11.9 pmol/l (8.5-112.3 pg/mL). It seems that elevation of serum PTH above this range can be considered as hyperparathyroidism in very low birth weight infants., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Mortality in hemodialysis (HD) patients remains unacceptably high compared with that of the general population and despite the continuous improvement of dialysis techniques. This study aimed to assess the role of alkaline phosphatase serum levels on cardiovascular and overall mortality in the RISCAVID study cohort through a long follow-up period, looking for associations with known risk factors for poor outcome., Methods: In June 2004, a prospective observational study was started focusing on the cardiovascular risk in hemodialysis patients who lived in the north-west area of Tuscany (RISCAVID, "RISchio CArdiovascolare nei pazienti afferenti all'Area Vasta In Dialisi"). The RISCAVID cohort included 572 prevalent patients on maintenance HD for at least three months. Morbid or fatal events were prospectively recorded at 6-month intervals for a follow up time of 216 months., Results: In univariable Cox regression analysis, dialysis technique, Geriatric Nutritional Risk Index, peripheral vascular disease, and intact parathyroid hormone and total calcium serum levels were significantly associated with baseline alkaline phosphatase serum levels. Cox multivariable analysis showed that elevated serum alkaline phosphatase levels (the highest quartile), advanced age, dialysis vintage, type of vascular access, Geriatric Nutritional Risk Index, C-reactive protein and calcium serum levels, history of cardiovascular disease and peripheral vascular disease were independent predictors of overall mortality in maintenance HD patients. The fourth quartile of alkaline phosphatase was associated with all-cause 10-year mortality (HR: 1.47; 95% CI: 1.177-1.834) with a 47% increase with respect to the 1st, 2nd, and 3rd quartiles. This was also observed for 18-year all-cause mortality., Conclusions: Adjusted proportional analysis showed the alkaline phosphatase value to be an independent and powerful predictor of overall mortality in the hemodialysis population., (© 2024. The Author(s).)

Background: There are about 7,000 rare diseases that affect 10% of the world population. Primary biliary cholangitis, an autoimmune chronic liver disease of the interlobular bile ducts, is one of the most common causes of chronic cholestasis. However, it is a rare, often underdiagnosed and undertreated, disease which can lead to cirrhosis and liver failure. We aimed to assess the proportion of undetected primary biliary cholangitis patients in primary care through a clinical management process., Methods: We made two extractions of the clinical data concerning liver diseases, risk factors and laboratory tests from the databases of a sample of general practitioners, with a check and correction of mistakes. The clinical data of the patients without liver disease and major risk factors, and with serum Alkaline Phosphatase above the laboratory reference values, were re-evaluated by each general practitioner with an expert gastroenterologist. The patients with elevated Alkaline Phosphatase values and without evidence of intrahepatic or extrahepatic causes of cholestasis were considered suspected for primary biliary cholangitis and assessed for antimitochondrial antibodies test and specialist' s evaluation, according to present guidelines., Results: A total of 20,480 adults attending 14 general practitioners in the province of Brescia, Northern Italy, were included in the study. Nine patients had a prior primary biliary cholangitis diagnosis, with a prevalence of 43.9/100000. After excluding 2094 (10.2%) patient with liver diseases or other causes of cholestasis, 121 subjects with Alkaline Phosphatase above the reference values were re-evaluated by the general practitioners and gastroenterologist, and 27 patients without symptoms or signs of cholestasis were considered suspected for primary biliary cholangitis: 9 of them were tested for antimitochondrial antibodies, and three new primary biliary cholangitis cases were detected (+33%)., Discussion and Conclusions: This study shows that there is a not negligible burden of undetected cases of adult rare diseases that can be diagnosed in primary care, through a disease management procedure, without modifying the routine clinical practice.

Atrazine (ATRA) and ciprofloxacin (CPRO) are widely detected, persistent and co-existing aquatic pollutants. This study investigated effects of 14-day single and joint ATRA and CPRO exposure on juvenile Clarias gariepinus. Standard bioassay methods were used to determine responses of oxidative stress, hepatic condition, and immunological biomarkers on days 7 and 14. Seven groups were used: Control, CPRO EC , CPRO Subl , ATRA EC , ATRA Subl , CPRO EC +ATRA EC , and CPRO Subl +ATRA Subl . The test substances caused decreased activity of superoxide dismutase, catalase, and glutathione peroxidase. Lipid peroxidation was elevated, especially in CPRO-ATRA mixtures. Serum aminotransferases (ALT, and AST), and alkaline phosphatase activity increased significantly. Total protein, albumin, total immunoglobulin, and respiratory burst decreased significantly. Therefore, single and joint exposure to CPRO and ATRA poses adverse consequences on aquatic life., Competing Interests: Declaration of Competing Interest The authors declare that there are no competing interests whatsoever., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: Prompted by an alarmingly low screening rate for metabolic bone disease of prematurity (MBDP), we aimed to increase MBDP screening with serum calcium, phosphorous, and alkaline phosphatase at four to six weeks of life in infants born at <1500 g and <32 gestational weeks from a baseline of 27.37% to 90% within one year., Study Design: We used the Institute for Healthcare Improvement's Model for Improvement as a framework. A key driver diagram informed the interventions which were carried out through four Plan-Do-Study-Act cycles., Results: There were 129 and 130 neonates in the pre-intervention baseline group and post-intervention MBDP bundle group, respectively. MBDP bundled primary screening rates increased from 27.37% to 95.56% (p < 0.001). Furthermore, 20% of infants had an individualized change in their enteral mineral supplementation after the initiative., Conclusions: An interdisciplinary team-based quality improvement approach was effective in altering clinical practice to improve screening and subsequent treatment for MBDP., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: This study aimed to analyze the diagnostic efficacy of serum biomarkers in liver cirrhosis patients categorized by Child-Pugh scores., Methods: An observational cross-sectional study design was employed. A total of 110 liver cirrhosis patients, classified according to Child-Pugh scores and 60 healthy individuals were included in this study. Serum levels of adenosine deaminase (ADA), adiponectin (APN), matrix metalloproteinase-2 (MMP-2), alkaline phosphatase (ALP), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were measured., Results: The levels of ADA, APN, MMP-2, ALP, ALT, and AST were significantly higher in the study group compared to the control group (P < .05). Furthermore, these levels increased with the severity of liver cirrhosis, with higher levels observed in patients with Child-Pugh class C. The positive diagnostic rates for joint detection in Child-Pugh class A, B, and C were 93.75% (30/32), 100% (34/34), and 100% (44/44), respectively., Conclusions: Combined detection of serum biomarkers improves the diagnostic efficacy of liver cirrhosis. The diagnostic rates were higher when considering Child-Pugh scores, with the highest rates observed in class C.

Purpose: To summarize the clinical and biochemical characteristics of patients with ceftriaxone-induced liver injury and guide the selection of safe medication., Methods: Retrieved domestic and foreign databases from inception to October 2023, collected case data conforming to ceftriaxone-induced liver injury, and statistically analyzed the data., Results: A total of 617 articles were retrieved, and 16 articles with 33 cases (10 children, 23 adults) were included. Males represented 60% (18/30), with a male-to-female ratio of 1.5:1. The age of onset ranged from 2 days to 96 years, with 15 of 23 adults (65%) over 55 years old. The time from ceftriaxone use to liver injury fluctuated between 0.5 and 47 days. Only 9 patients (27.3%, 9/33) had clinical symptoms, and the clinical classification was dominated by cholestatic injury (46.2%, 12/26). There was a significant difference in the clinical classification of ceftriaxone-induced liver injury between children and adults (P = 0.0126), with hepatocellular injury predominating in children and cholestatic injury predominating in adults. The severity of liver injury was mainly mild (66.7%, 12/18). Peak values of alanine aminotransferase ranging from 228.5 to 8098 U/L, aspartate aminotransferase ranging from 86.7 to 21575 U/L, alkaline phosphatase ranging from 143 to 2434 U/L, and total bilirubin ranging from 3.35 to 66.1 mg/dL. There was a significant difference in peak values of alkaline phosphatase between children and adults (P = 0.027), with a higher peak value of alkaline phosphatase in adults (1039 ± 716.4 U/L vs. 257 ± 134.9 U/L). Patients with normal imaging examinations accounted for the majority (61.5%, 7/13). The prognosis of 32 patients (97%, 32/33) was good, and one child with sickle cell anemia who developed immune hemolysis, progressive renal failure, and acute liver injury after using ceftriaxone died in the end., Conclusion: Ceftriaxone-induced liver injury can occur at any age, with a higher risk in the elderly, and age may be related to the clinical classification. Although the clinical manifestations are not specific, close monitoring of liver biochemical indicators during the use can detect liver injury early. Most cases have a good prognosis, but for people with concomitant sickle cell anemia, it is necessary to be vigilant about the occurrence of severe hemolytic anemia., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Activin A has been shown to enhance osteoclast activity and its inhibition results in bone growth. The potential role of activin A as a marker of chronic kidney disease-mineral bone disease (CKD-MBD) and its relationship with other markers has not been studied in children with CKD., Methods: A cross sectional study was conducted among 40 children aged 2 to 18 years with CKD (Stage 2 to 5; 10 in each stage) and 40 matched controls. Activin A, cathepsin K, FGF-23, PTH, serum calcium, phosphorous and alkaline phosphatase in both groups were measured and compared. The correlation of activin A and markers of CKD-MBD was studied. A p value of < 0.05 was considered significant., Results: The mean age of children with CKD was 9.30 ± 3.64 years. Mean levels of activin A in cases were 485.55 pg/ml compared to 76.19 pg/ml in controls (p < 0.001). FGF-23 levels in cases were 133.18 pg/ml while in controls it was 6.93 pg/ml (p < 0.001). Mean levels of cathepsin K were also significantly higher in cases as compared to controls. There was a progressive increase in activin A and cathepsin K levels with increasing stage of CKD. Activin A had a significant positive correlation with serum creatinine (r = 0.51; p < 0.001)., Conclusions: Activin A levels progressively rise with advancing CKD stage. These findings suggest that activin A can be a potential early marker of CKD-MBD in children., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

BACKGROUND Long-term clinical practice has suggested a possible association between ossification of cervical ligament (OCL) and primary osteoporosis (POP). However, there is a lack of relevant research data. This study aimed to clarify the potential relationship between OCL and POP, and propose new strategies for preventing the onset of POP. MATERIAL AND METHODS The study involved 107 patients. The patients' diagnosis included OCL (ossification of the posterior longitudinal ligament, ossification of the ligamentum flavum, and ossification of the nuchal ligament) and POP. Bone mineral density (BMD), types of OCL, types of ossification of posterior longitudinal ligament, age, sex, serum calcium, serum phosphorus, alkaline phosphatase, type I collagen amino-terminal extension peptide, type I collagen degradation products, osteocalcin N-terminal molecular fragments, 25-hydroxyvitamin D, and history of taking steroid drugs were collected. SPSS24.0 and GraphPad Prism 8 were used to obtain the risk factors for POP. RESULTS One-way analysis of variance found that OCL, ossification of posterior longitudinal ligament, alkaline phosphatase, and osteocalcin N-terminal molecular fragments had statistical significance on BMD of the femoral neck (P<0.05). The independent sample t test showed that patient sex had statistical significant effect on BMD (femoral neck) (P=0.036). Incorporating the above factors into multiple linear regression analysis, it was found that OCL, alkaline phosphatase, and osteocalcin N-terminal molecular fragments were risk factors affecting BMD of femoral neck (P<0.05). CONCLUSIONS OCL, osteocalcin N-terminal molecular fragments, and alkaline phosphatase are risk factors for POP.

The consumption of mushrooms containing α-Amanitin (α-A) can lead to severe liver damage. In this study, toxicological experiments were conducted to confirm the protective effects of pomegranate seed oil (PSO) and black cumin oil (BCO) against α-A-induced hepatotoxicity. Rats exposed once to α-A (3 mg/kg bw, i.p.) or saline alone (0.1 ml, i.p.) were either left untreated or treated with PSO or BCO at a dose of 2 ml/kg bw/day by oral gavage on the same day, and the treatment was continued for 7 days. Serum aminotransferases (ALT and AST), alkaline phosphatase (ALP) and total protein levels were measured and the active caspase 3 (cl-caspase 3) was evaluated by western blotting in the liver. Serum ALT, AST and ALP levels tended to decrease in the α-A exposed group, but no statistically significant difference was found compared to the saline group (p > 0.05). PSO and BCO did not affect serum liver function tests in rats exposed to saline or α-A. α-A toxicity was demonstrated by a significant decrease in serum total protein level (p < 0.05), a significant increase in liver cl-caspase 3 expression (p < 0.05), and structural liver damage mainly characterized by mononuclear inflammation and steatosis. When α-A exposed rats were treated with BCO, the increase in cl-caspase 3 was not inhibited, on the contrary BCO increased cl-caspase 3 in healthy rats (p < 0.05). PSO significantly ameliorated α-A-induced cl-caspase 3 increase and inflammatory histopathology in the liver. Both PSO and BCO completely prevented α-A-induced protein degradation. The findings indicate that PSO and BCO may protect liver functions against α-A-induced hepatotoxicity, encouraging future comprehensive studies to test them at different doses and frequency., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Despite therapy with growth hormone (GH) in children with Prader-Willi syndrome (PWS), low bone mineral density and various orthopedic deformities have been observed often. Therefore, this study aimed to analyze bone markers, with an emphasis on vitamin K-dependent proteins (VKDPs), in normal-weight children with PWS undergoing GH therapy and a low-energy dietary intervention. Twenty-four children with PWS and 30 healthy children of the same age were included. Serum concentrations of bone alkaline phosphatase (BALP), osteocalcin (OC), carboxylated-OC (Gla-OC), undercarboxylated-OC (Glu-OC), periostin, osteopontin, osteoprotegerin (OPG), sclerostin, C-terminal telopeptide of type I collagen (CTX-I), and insulin-like growth factor-I (IGF-I) were determined using immunoenzymatic methods. OC levels and the OC/CTX-I ratios were lower in children with PWS than in healthy children ( p = 0.011, p = 0.006, respectively). Glu-OC concentrations were lower ( p = 0.002), but Gla-OC and periostin concentrations were higher in patients with PWS compared with the controls ( p = 0.005, p < 0.001, respectively). The relationships between IGF-I and OC ( p = 0.013), Gla-OC ( p = 0.042), and the OC/CTX-I ratio ( p = 0.017) were significant after adjusting for age in children with PWS. Bone turnover disorders in children with PWS may result from impaired bone formation due to the lower concentrations of OC and the OC/CTX-I ratio. The altered profile of OC forms with elevated periostin concentrations may indicate more intensive carboxylation processes of VKDPs in these patients. The detailed relationships between the GH/IGF-I axis and bone metabolism markers, particularly VKDPs, in children with PWS requires further research.

Acitretin, commonly used for severe psoriasis and keratinocyte carcinoma chemoprevention in high-risk patients, is contraindicated in patients with end-stage renal disease (ESRD) on haemodialysis (HD). However, these patients often lack medication choices and in certain clinical scenarios the benefits of acitretin may outweigh the potential risks. We identified 24 patients with ESRD on HD undergoing acitretin treatment from the Duke and Vanderbilt University Medical Centers. While adverse effects were common, they were not a frequent cause of treatment discontinuation among patients. We also found no association between acitretin treatment and hospital admissions or mortality. Lastly, we found statistically significant increases in alkaline phosphatase (ALP; P = 0.03) and total bilirubin (P < 0.001) when patients were receiving acitretin and HD compared with baseline. However, there was no dose dependency or temporal association with acitretin or HD initiation. Based on these preliminary findings, we find that acitretin may safely be used in patients receiving HD, with close monitoring of ALP and bilirubin., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

&lt;b&gt;Introduction:&lt;/b&gt; Colorectal cancer (CRC) prognosis is typically determined based on clinical stage and histopathological findings, yet patients with the same stage and histological structure can exhibit varying survival outcomes. This highlights the need for additional prognostic biomarkers. Serum biomarkers are gaining increasing significance due to their affordability and accessibility. The albumin-alkaline phosphatase ratio (AAPR) has been associated with prognosis in hepatocellular and gastric cancers, but its role in CRC remains underexplored.&lt;b&gt;Aim:&lt;/b&gt; This study aimed to evaluate the effect of the albumin-alkaline phosphatase ratio (AAPR) on the prognosis of patients with colorectal cancer (CRC).&lt;b&gt;Material and method:&lt;/b&gt; Data from 358 patients who had undergone surgery for CRC were analyzed retrospectively to identify factors that could predict overall survival (OS). The Roc-Curve test was applied to determine the power of the preoperative AAPR in predicting mortality. Kaplan Meier and log-rank tests were used to examine the survival times of the patients.&lt;b&gt;Results:&lt;/b&gt; Our findings revealed that an albumin-alkaline phosphatase cut-off ratio above 0.67 predicted mortality with a sensitivity of 17.54% and a specificity of 92.22%. Although patients with a lower AAPR exhibited a slightly shorter mean survival time compared to those above the cut-off value, this difference did not reach statistical significance (P = .112).&lt;b&gt;Conclusions:&lt;/b&gt; The results of this study did not provide evidence to support the AAPR as a potential prognostic factor in patients with colorectal cancer.

Purpose: Using ex vivo normothermic machine perfusion (NMP) with whole blood we assessed marginal porcine kidneys under reperfusion. The aim was to link measureable machine and clinical blood parameters with the currently used visual assessment. This could serve as a baseline for a standardized evaluation score to identify potentially transplantable kidneys in the future., Methods: Kidneys and autologous whole blood were procured from slaughterhouse pigs (n = 33) and were perfused for 4 h using NMP. The hemodynamic parameters arterial pressure (AP), renal blood flow (RBF) and intrarenal resistance (IRR) were measured. Activity of aspartate transaminase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and lactate were assessed in blood at 0/1/2/4 h. Kidneys were grouped into "potentially transplantable" (PT) or "not transplantable" (NT) based on their overall macroscopic appearance after NMP by an experienced physician., Results: PT-kidneys (n = 20) had a significantly lower IRR and higher RBF than NT-kidneys (n = 13). GGT, ALP and LDH did not differ significantly, but at 4 h, AST was significantly higher in PT-kidneys compared to NT-kidneys. Lactate levels kept increasing during NMP in NT-kidneys and were significantly higher at 1/2/4 h than in PT-kidneys., Conclusion: The immediately assessed macroscopic aspects of examined kidneys correlated with hemodynamic parameters, increased lactate and lower AST in this study. In the future, NMP with whole blood could be a useful tool to extend the donor pool by allowing the assessment of otherwise unknown characteristics of marginal kidneys before transplantation., (© 2024. The Author(s).)

Parenteral nutrition (PN) is a life-sustaining method to provide adequate nutrients to patients unable to receive oral or enteral nutrition. PN typically contains a mixture of macro- and micro-nutrients, although the lipid composition has been identified as a concern for liver disease. Therefore, the study of the intravenous lipid emulsion (ILE) prescribing practices in home-based PN (HPN) patients and whether differing lipid PN alters liver function tests (LFTs) is needed., Methods: A retrospective study of monthly LFTs from a random sample of 105 adult HPN patients in the U.S. over a 6-month period was conducted. Patients were receiving olive oil/soy oil (n = 53, Clinolipid), mixed ILE (n = 39, SMOF Lipid), soy oil (SO; n = 4, Intralipid), or none (n = 7). LFTs monitored were alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (T Bili)., Results: No differences were observed in baseline LFTs across groups (all, p > 0.25, η 2 < 0.04), nor were there differences in age, body mass index, days of PN, or mean PN volume (all, p > 0.36, η 2 < 0.05). There were no significant interactions between ILE type and time (all p > 0.64, η p 2 < 0.03), no effect of ILE type (all p > 0.60, η p 2 < 0.03), and no effect of time (all p > 0.69, η p 2 < 0.01) in terms of LFTs. Average LFTs over six months were also not different between ILE types (all p > 0.30, η 2 < 0.04)., Conclusion: These findings suggested that patients were mostly prescribed mixed or ILE PN containing more than one lipid source and that differing ILEs in long-term HPN patients did not alter LFTs over a six-month period.

Introduction: Effective tools to evaluate bone quality preoperatively are scarce and the standard method to determine bone quality requires an invasive biopsy. A non-invasive, and preoperatively available method for bone quality assessment would be of clinical value. The purpose of this study is to investigate the associations of bone formation marker, serum bone alkaline phosphatase (BAP), and bone resorption marker, urine collagen cross-linked N-telopeptide (uNTX) to volumetric bone mineral density (vBMD), fluorescent advanced glycation endproducts (fAGEs) and bone microstructure., Materials and Methods: A cross-secional analysis using prospective data of patients undergoing lumbar spinal fusion was performed. BAP and uNTX were preoperatively collected. Quantitative computed tomography (QCT) was performed at the lumbar spine (vBMD ≤ 120 mg/cm 3 osteopenic/osteoporotic). Bone biopsies from the posterior superior iliac spine were obtained and evaluated with multiphoton fluorescence microscopy for fAGEs and microcomputed tomography (µCT) for bone microarchitecture. Correlations between BAP/uNTX to vBMD, fAGEs and µCT parameters were assessed with Spearman's ρ. Receiver operating characteristic (ROC) analysis evaluated BAP and uNTX as predictors for osteopenia/osteoporosis. Multivariable linear regression models adjusting for age, sex, BMI, race and diabetes mellitus determined associations between BAP/uNTX and fAGEs., Results: 127 prospectively enrolled patients (50.4% female, 62.5 years, BMI 28.7 kg/m 2 ) were analyzed. uNTX (ρ=-0.331,p < 0.005) and BAP (ρ=-0.245,p < 0.025) decreased with cortical fAGEs, and uNTX (ρ=-0.380,p < 0.001) decreased with trabecular fAGEs. BAP and uNTX revealed no significant correlation with vBMD. ROC analysis for BAP and uNTX discriminated osteopenia/osteoporosis with AUC of 0.477 and 0.561, respectively. In the multivariable analysis, uNTX decreased with increasing trabecular fAGEs after adjusting for covariates (β = 0.923;p = 0.031)., Conclusion: This study demonstrated an inverse association of bone turnover markers and fAGEs. Both uNTX and BAP could not predict osteopenia/osteoporosis in the spine. uNTX reflects collagen characteristics and might have a complementary role to vBMD, as a non-invasive tool for bone quality assessment in spine surgery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background and Aims: The role of aortic mineralization in the pathogenesis of acute type B aortic dissection (TBAD) is unclear. Whether thoracic aortic calcification (TAC) and circulating alkaline phosphatase (ALP) activity are associated with acute TBAD risk remains elusive., Methods: Observational and Mendelian randomization (MR) studies were conducted sequentially. Using propensity score matching (1:1) by age and sex, patients with acute TBAD (n = 125) were compared with control patients (n = 125). Qualitative (score) and quantitative (volume) analyses of the TAC burden on different thoracic aortic segments were conducted using non-enhanced computed tomography. Univariate and multivariate analyses were used to identify significant independent risk factors for TBAD and TAC burden, respectively. MR was finally used to determine the causal relationship between elevated ALP activity and TBAD risk., Results: The qualitative and quantitative analyses revealed that TAC burden was significantly higher in the TBAD group, except for in the ascending aortic segment (both p < 0.05). Preoperative circulating ALP was significantly elevated in the TBAD group (p < 0.001). The elevated TAC burden score on the descending thoracic aortic segment (odds ratio [OR] 3.31, 95% confidence interval [CI] 1.31-8.37) and increased ALP activity (OR 1.03, 95% CI 1.01-1.06) was independently associated with TBAD risk. Interestingly, ALP was significantly positively associated with TAC burden, and MR analyses confirmed that ALP genetically predicted TBAD risk., Conclusions: Elevated ALP may trigger TBAD risk via the increased volume of TAC. Aortic mineralization may not protect the aorta itself., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This study aimed to evaluate the association between maternal liver biomarkers in early pregnancy and the risk of hypertensive disorders of pregnancy (HDP), as well as to evaluate interaction between liver enzymes and BMI on the development of HDP. Pregnant women in our study were recruited from the Zhoushan Pregnant Women Cohort. Participants who had their first prenatal follow-up and the blood pressure follow-up records, and measured liver biomarkers in the first trimester were eligible for inclusion in the study. A total of 10,610 pregnant women were included in the analysis, and 305 (2.87%) developed the HDP. There were positive associations between AST, GGT, ALP, HSI and SBP, as well as between ALT, GGT, ALP, HSI and DBP. In addition, AST/ALT level was negatively associated with DBP. The highest quartile of GGT, ALP, AST/ALT and HSI were significantly associated with 1.71-fold (95% Cl: 1.23-2.41), 1.53-fold (95% Cl: 1.10-2.14), 0.62-fold (95% Cl: 0.43-0.90) and 1.67-fold (95% Cl: 1.05-2.67) increased risk of HDP, respectively. There was no significant association between ALT, AST and HDP. These associations remained consistent in pregnant women with liver enzymes within the clinical reference range. Besides, we found an interaction between GGT and BMI (P interaction  = 0.013) in the development of HDP. In summary, the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP, even within the clinical reference range. And there was an interaction between liver biomarkers and BMI in the development of HDP. Our study showed the level of GGT, ALP, AST/ALT and HSI were associated with the subsequent risk of HDP. And there was an interaction between GGT and BMI in the risk of HDP., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Background: Alkaline phosphatase (ALP) is an enzyme which has been proven useful as a biomarker for bone turnover and inflammation. We hypothesized that high serum ALP levels are associated with increased complication rates following lumbar spinal fusion., Methods: Lumbar spinal fusion procedures from 2005 to 2019 were queried from the National Surgical Quality Improvement Program (NSQIP) database. Serum alkaline phosphatase levels were stratified into low <44 IU/L, normal 44-147 IU/L, and high >147 IU/L. A risk-adjusted multivariate logistic regression was used to analyze ALP as an independent risk factor for complications., Results: A total of 16,441 patients who underwent lumbar fusion procedures were included. Adjusted multivariate logistic regression analysis demonstrated that patients with a high serum ALP level had a significantly increased risk for developing septic shock (OR 4.68, 95% CI 1.83-11.97), pneumonia (OR 2.89, 95% CI 1.59-5.25), requiring a transfusion (OR 2.09, 95% CI 1.68-2.59), reoperation within 30 days (OR 1.68, 95% CI 1.12-2.52), readmission within 30 days (OR 1.60, 95% CI 1.16-2.21), increased length of stay (OR 1.87, 95% CI 1.49-2.36), and nonhome discharge (OR 2.18, 95% CI 1.80-2.66)., Conclusions: Elevated serum ALP in patients undergoing lumbar fusion procedures is associated with increased risk for multiple in-hospital complications as well as higher rates of readmission and reoperation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Aim: Lenvatinib mesylate (LEN) is an oral tyrosine kinase inhibitor used to treat various cancers, including hepatocellular carcinoma (HCC). HCC treatment with LEN is associated with a very high incidence of adverse events. This study was aimed at investigating the incidence of LEN-induced palmar-planter erythrodysesthesia syndrome (PPES) and its relationship with patient demographics by analyzing clinical laboratory data of LEN-treated patients with HCC., Methods: This was a single-centre, retrospective study of patients with HCC who received LEN between April 19, 2018, and September 30, 2020. The observation period was from 1 week before the start of LEN administration to 1 month after the end of administration., Results: Overall, 75 patients with HCC were enrolled. LEN-induced PPES was found in 48.0% (36/75 patients). In these patients, alkaline phosphatase (ALP), γ-Glutamyl transpeptidase (γ-GTP) and monocytes (MONO) were significantly high (ALP: p = 1.32 × 10 -3 , γ-GTP: p = 4.25 × 10 -3 and MONO: p = 0.013). The cut off values of ALP, γ-GTP and MONO for LEN-induced PPES were estimated at 573 U/L, 89 U/L, and 310 counts/μL, respectively. In the multivariate analysis, γ-GTP and MONO were independent risk factors for LEN-induced PPES., Conclusions: High γ-GTP and high MONO were risk factors for LEN-induced PPES., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Elevated alkaline phosphatase (ALP) levels are found in multiple hepatobiliary diseases and in bone diseases. ALP can also originate in the intestine and placenta. Very few cases of persistent elevations of IALP or in the context of benign familial intestinal hyperphosphatasemia (BFIH) without underlying pathology have been reported in the literature. In the evaluation of elevated ALP, most patients will not require determination of its isoenzymes. However, it is important to be aware of this entity to avoid unnecessary additional studies and to establish the diagnosis of a persistent but benign biochemical abnormality.

Background: The health risk associated with acrylamide exposure has emerged as a significant issue of public health, attracting global attention. However, epidemiologic evidence on whether and how daily acrylamide exposure increases depression risk of the general population is unclear., Methods: The study included 3991 adults from the National Health and Nutrition Examination Survey. The urinary metabolites of acrylamide (N-Acetyl-S-(2-carbamoylethyl)-L-cysteine [AAMA] and N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine [GAMA]) identified as reliable indicators of acrylamide exposure were examined to determine their relationships with depressive symptoms that were evaluated using the 9-item Patient Health Questionnaire. Besides, the measurements of alkaline phosphatase (ALP) and biomarkers of inflammation (white blood cell [WBC] count) and anti-oxidative stress (albumin [ALB]) were conducted to investigate their mediation roles in above relationships., Result: AAMA, GAMA, and ΣUAAM (AAMA+GAMA) were linearly associated with increased risk of depressive symptoms. Each 2.7-fold increase in AAMA, GAMA, or ΣUAAM was associated with a 30 % (odds ratio: 1.30; 95 % confidence interval: 1.09, 1.55), 47 % (1.47; 1.16, 1.87), or 36 % (1.36; 1.13, 1.63) increment in risk of depressive symptoms, respectively. Increased WBC count (mediated proportion: 4.48-8.00 %), decreased ALB (4.88-7.78 %), and increased ALP (4.93-5.23 %) significantly mediated the associations between acrylamide metabolites and depressive symptoms., Conclusions: Acrylamide exposure of the general adult population was related to increased risk of depressive symptoms, which was mediated in part by inflammation, oxidative stress, and increased ALP. Our findings provided pivotal epidemiologic evidence for depression risk increment from exposure to acrylamide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Osteoporosis in pre-dialysis chronic kidney disease (CKD) patients has been overlooked, and the risk factors of osteoporosis in these patients have not been adequately studied., Objective: To identify risk factors for osteoporosis in pre-dialysis CKD patients and develop predictive models to estimate the likelihood of osteoporosis., Methods: Dual-energy X-ray absorptiometry was used to measure bone mineral density, and clinical examination results were collected from 326 pre-dialysis CKD patients. Binary logistic regression was employed to explore the risk factors associated with osteoporosis and develop predictive models., Results: In this cohort, 53.4% ( n  = 174) were male, 46.6% ( n  = 152) were female, and 21.8% ( n  = 71) were diagnosed with osteoporosis. Among those diagnosed with osteoporosis, 67.6% ( n  = 48) were female and 32.4% ( n  = 23) were male. Older age and low 25-(OH)-Vitamin D levels were identified as risk factors for osteoporosis in males. For females, older age, being underweight, higher bone alkaline phosphatase (NBAP), and advanced CKD (G5) were significant risk factors, while higher iPTH was protective. Older age, being underweight, and higher NBAP were risk factors for osteoporosis in the G1-4 subgroup. In the G5 subgroup, older age and higher NBAP increased the risk, while high 25-(OH)-Vitamin D or iPTH had protective effects. Nomogram models were developed to assess osteoporosis risk in pre-dialysis patients based on gender and renal function stage., Conclusion: Risk factors for osteoporosis vary by gender and renal function stages. The nomogram clinical prediction models we constructed may aid in the rapid screening of patients at high risk of osteoporosis.

This work addresses challenges of simple but reliable determination of enzyme alkaline phosphatase (ALP) in μL-sized serum samples. The single-tube assay and plate-based immunoassay were developed by using a commercial glucose test strip (GTS) to transduce analytical signal from the ALP + glucose-6-phosphate (G6P) reaction. The glucose released from G6P contributed to the flow of anodic charge Q 20s through GTS. The interferences from serum matrix including those from native glucose were eliminated by devising a signal ΔQ 20s  = Q 20s (total) - Q 20s (matrix) . The ΔQ 20s was proportional to ALP activity within a linear range of 7.4-720 IU L -1 for assay (R 2 , 0.995) and 10-300 IU L -1 for immunoassay (R 2 , 0.983), which far exceeded a normal clinical range for ALP in adult human serum (30-150 IU L -1 ). Both methods required no auxiliary enzymes or labels, and were accurate (93-99 % signal recovery) and precise (RSD ≤10%). The assay was a simpler option because it required only one 20-min incubation step to determine ALP. The immunoassay involved three steps but it was still less laborious (by ∼70%) than a traditional enzyme-linked immunosorbent assay (ELISA) of ALP due to the substitution of ELISA detection antibody with GTS. The GTS-G6P-based methods bring ALP testing closer to the point-of-care locations, which is important considering the growing role of ALP as a prophylactic, therapeutic, and anti-inflammatory agent, and a marker of human diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Abnormal alkaline phosphatase (ALP) levels have been linked to breast cancer, prostate cancer, bone damage, gingivitis and abnormal liver function. Monitoring ALP levels is important for better diagnosis and treatment of these diseases. Detection of ALP by colorimetric methods is very portable in terms of signal reading, but still suffers from low sensitivity. SERS can achieve high sensitivity detection, but cannot be separated from large precision instruments. Therefore, researchers have worked to optimize various aspects of the sensor, such as sensitivity, detection time, and operating procedures, to enable portable and rapid ALP detection. Isothermal amplification using simple system components meets the current demand for rapid, portable assays. We have developed a novel one-pot high-efficiency ALP assay strategy called IHP-GT. IHP-GT performs a one-step cascade amplification using only one probe (IGHP) as a template. The phosphorylated primer P binds to IGHP, forming a P/IGHP structure. At this point, the G-quadruplex closes and no signal is generated. In the presence of ALP, primer P is dephosphorylated to remove the restriction and then amplified in a cascade using IGHP as a template to release the full G-quadruplex structure. The single-stranded G-quadruplex will bend to form a secondary structure, facilitating secondary amplification starting with primer AT to produce PrG and P'. The PrG structure will trigger triple amplification, enabling cascade amplification. The G-quadruplex structure produced by cascade amplification has the dual role of promoting amplification of primer AT and binding to ThT to produce a fluorescent signal. The IHP-GT method provides a highly sensitive detection of ALP in less than 90 min and has been successfully used to analyze ALP in human serum samples. In addition, IHP-GT can be used to screen for ALP inhibitors. Importantly, we lyophilized the IHP-GT reaction components into powder form for user-friendly poc testing., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

As of 2023, more than 200 million people worldwide are living with osteoporosis. Oral bisphosphonates (BPs) are the primary treatment but can cause gastrointestinal (GI) side effects, reducing patient compliance. Microarray (MAP) technology has the potential to overcome GI irritation by facilitating the transdermal delivery of BPs. This study examines the delivery of alendronic acid (ALN) and risedronate sodium (RDN) using dissolving and hydrogel-forming MAPs for osteoporosis treatment. In vivo testing on osteoporotic female Sprague Dawley rats demonstrated the efficacy of MAPs, showing significant improvements in mean serum and bone alkaline phosphatase levels, bone volume, and porosity compared to untreated bilateral ovariectomy (OVX) controls. Specifically, MAP treatment increased mean bone volume to 55.04 ± 2.25 % versus 47.16 ± 1.71 % in OVX controls and reduced porosity to 44.30 ± 2.97 % versus 52.84 ± 1.70 % in the distal epiphysis of the femur. In the distal metaphysis, bone volume increased to 43.32 ± 3.24 % in MAP-treated rats compared to 24.31 ± 3.21 % in OVX controls, while porosity decreased to 55.39 ± 5.81 % versus 75.69 ± 3.21 % in OVX controls. This proof-of-concept study indicates that MAP technology has the potential to be a novel, patient-friendly alternative for weekly osteoporosis management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Nanoceria have demonstrated a wide array of catalytic activity similar to natural enzymes, holding considerable significance in the colorimetric detection of alkaline phosphatase (ALP), which is a biomarker of various biological disorders. However, the issues of physiological stability and formation of protein corona, which are strongly related to their surface chemistry, limit their practical application. In this work, CeO 2 nanoparticles characterized by enhanced dimensional uniformity and specific surface area were synthesized, followed by encapsulation with various polymers to further increase catalytic activity and physiological stability. Notably, the CeO 2 nanoparticles encapsulated within each polymer exhibited improved catalytic characteristics, with PAA-capped CeO 2 exhibiting the highest performance. We further demonstrated that the PAA-CeO 2 obtained with enhanced catalytic activity was attributed to an increase in surface negative charge. PAA-CeO 2 enabled the quantitative assessment of AA activity within a wide concentration range of 10 to 60 μM, with a detection limit of 0.111 μM. Similarly, it allowed for the evaluation of alkaline phosphatase activity throughout a broad range of 10 to 80 U/L, with a detection limit of 0.12 U/L. These detection limits provided adequate sensitivity for the practical detection of ALP in human serum., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Purpose: Secondary opportunistic coinfections are a significant contributor to morbidity and mortality in intensive care unit (ICU) patients, but can be difficult to identify. Presently, new blood RNA biomarkers were tested in ICU patients to diagnose viral, bacterial, and biofilm coinfections. Methods: COVID-19 ICU patients had whole blood drawn in RNA preservative and stored at -80°C. Controls and subclinical infections were also studied. Droplet digital polymerase chain reaction (ddPCR) quantified 6 RNA biomarkers of host neutrophil activation to bacterial (DEFA1), biofilm (alkaline phosphatase [ALPL], IL8RB/CXCR2), and viral infections (IFI27, RSAD2). Viral titer in blood was measured by ddPCR for SARS-CoV2 (SCV2). Results: RNA biomarkers were elevated in ICU patients relative to controls. DEFA1 and ALPL RNA were significantly higher in severe versus incidental/moderate cases. SOFA score was correlated with white blood cell count (0.42), platelet count (-0.41), creatinine (0.38), and lactate dehydrogenase (0.31). ALPL RNA (0.59) showed the best correlation with SOFA score. IFI27 (0.52) and RSAD2 (0.38) were positively correlated with SCV2 viral titer. Overall, 57.8% of COVID-19 patients had a positive RNA biomarker for bacterial or biofilm infection. Conclusions: RNA biomarkers of host neutrophil activation indicate the presence of bacterial and biofilm coinfections in most COVID-19 patients. Recognizing coinfections may help to guide the treatment of ICU patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: TM and TJ have an equity interest in True Bearing Diagnostics, Inc., a diagnostics company developing RNA biomarkers for various diseases, including coronary artery disease and internal infections.